Lgl1 deficiency disrupts hippocampal development and impairs cognitive performance in mice

Abstract

Cellular polarity is crucial for brain development and morphogenesis. Lethal giant larvae 1 (Lgl1) plays a crucial role in the establishment of cell polarity from Drosophila to mammalian cells. Previous studies have found the importance of Lgl1 in the development of cerebellar, olfactory bulb, and cerebral cortex. However, the role of Lgl1 in hippocampal development during the embryonic stage and function in adult mice is still unknown. In our study, we created Lgl1‐deficient hippocampus mice by using Emx1‐Cre mice. Histological analysis showed that the Emx1‐Lgl1−/− mice exhibited reduced size of the hippocampus with severe malformations of hippocampal cytoarchitecture. These defects mainly originated from the disrupted hippocampal neuroepithelium, including increased cell proliferation, abnormal interkinetic nuclear migration, reduced differentiation, increased apoptosis, gradual disruption of adherens junctions, and abnormal neuronal migration. The radial glial scaffold was disorganized in the Lgl1‐deficient hippocampus. Thus, Lgl1 plays a distinct role in hippocampal neurogenesis. In addition, the Emx1‐Lgl1−/− mice displayed impaired behavioral performance in the Morris water maze and fear conditioning test.

Role of LGL1 in cerebellar primordium of embryonic mice

“…In 1967, Schneiderman and Gattiff reported on the rapid proliferation and invasion of cells observed in drosophila mutation, which was considered to be a form of malignant tumor [12]. Loss of Lethal giant larvae (D-Lgl) in Drosophila melanogaster leads to disruption of apical-basal polarity, defects in epithelial structure, and uncontrolled cell proliferation [7,13,14]. However, it remains unclear whether Lgl1 is involved in carcinogenesis in higher eukaryotes.…”

“…of apical-basal polarity, defects in epithelial structure, and uncontrolled cell proliferation [7,13,14]. However, it remains unclear whether Lgl1 is involved in carcinogenesis in higher eukaryotes.…”

“…Samples were blocked with 5% (vol/vol) normal goat serum in PBS and incubated with primary antibodies including rabbit anti-Hugl-1 (Santa Cruz, Heidelberg, Germany, 1:50). This antibody was characterized in our previous studies [6][7][8], employed to detect the mouse homologue Lgl-1. Mouse anti-Nestin (Chemicon, Temecula, CA, USA, 1:200), rabbit anti-Cdc42 (Proteintech, Wuhan, China, 1:500), mouse anti-β-catenin (Proteintech, 1:300).…”

Lethal giant larvae gene is required for normal nymphal development and midgut morphogenesis in Locusta migratoria

“…Expression of a Drosophila l(2)gl cDNA in the sop1Δsop2Δ strain partially restored the Na + tolerance of the cells, indicating a novel function in cell homeostasis for this family of proteins extending from yeast to human (Larsson et al ., 1998). A recent study has shown that Lgl1 ‐deficient mice exhibited a disrupted hippocampal neuroepithelium, including increased cell proliferation, abnormal interkinetic nuclear migration, reduced differentiation, increased apoptosis, gradual disruption of adherens junctions, and abnormal neuronal migration (Zhang et al ., 2019). Lgl1 is also required for asymmetric cortical localization of all known basal determinants in mitotic neuroblasts (Peng et al ., 2000).…”

Altered Expression of Par3, aPKC-λ, and Lgl1 in Hippocampus in Kainic Acid-Induced Status Epilepticus Rat Model

“…Lethal giant larvae 1 (Lgl1) was initially known as a tumor suppressor ( 24 ) and regulator of polarization processes in variety of cells ( 25 , 26 ). It has been confirmed that Lgl1 is enriched in developing axons, and upregulation of Lgl1, which has promoted the axonal growth during neuronal morphogenesis ( 27 ).…”